Project Summary Nasal sinus disease is one of the most common medical conditions in the US, affecting an estimated 13% of adults, or more than 29 million people. Nasal obstruction and smell loss are two of the major symptoms of the disease; however, the field currently lacks a clear, objective understanding to the mechanisms causing these symptoms, which limits effective disease management. For example, patients' complaints of nasal obstruction correlate poorly or inconsistently with objective measurements of actual physical obstruction. Olfactory loss has been widely believed to be induced in part by airflow blockage; however, no tool has been able to quantify or predict such a mechanism. We propose to develop and validate a novel objective diagnostic tool for nasal obstructive symptoms, based on two hypotheses (a) that perception of nasal obstruction (lack of patency) is due to lack of nasal cooling caused by physical nasal conditions, and/or inadequate sensory feedback, and (b) that insufficient conduction of air/odorant flow specifically to the olfactory region contributes to olfactory losses. To test these hypotheses and pursue a clinical tool, we will conduct a study and focus on three aims. In Aim 1, we will use individualized computational fluid dynamics (CFD) nasal models based on patient CT scans to assess insufficient mucosal cooling due to existing airway abnormalities, and determine if this correlates with patient symptom ratings. We will further perturb patients' nasal airway temporarily with a nasal dilator and decongestant and test whether our approach can predict perceptual symptom changes. In Aim 2, we will broadly assess the trigeminal cool sensitivity of patients with the symptom of nasal obstruction, and determine whether abnormal trigeminal cool sensitivity (including the TRPM8 pathway) contributes to symptoms. TRPM8 is a major component of the cool afferent pathway that is also activated chemically, which offers a unique dual investigatory tool and potentially broadens our understanding of chemosensory functions in nasal inflammatory disease. In Aim 3, we will specifically target nasal polyp patients with olfactory losses, track their treatment progress, and determine if the CFD-predicted air transport and odorant sorption rate to the olfactory region correlate with olfactory function losses and recovery. The outcomes from this research may validate how to combine one or several measurements into an effective clinical tool to differentiate the causal factors leading to a patient's conductive symptoms, to potentially identify the site that most affects the symptom, and to guide move effective treatment or surgery in the future.